Highly Activated Terminal Carbon Monoxide Ligand in an Iron–Sulfur Cluster Model of FeMco with Intermediate Local Spin State at Fe

Nitrogenases, the enzymes that convert N2 to NH3, also catalyze the reductive coupling of CO to yield hydrocarbons. CO-coordinated species of nitrogenase clusters have been isolated and used to infer mechanistic information. However, synthetic FeS clusters displaying CO ligands remain rare, which limits benchmarking. Starting from a synthetic cluster that models a cubane portion of the FeMo cofactor (FeMoco), including a bridging carbyne ligand, we report a heterometallic tungsten–iron–sulfur cluster with a single terminal CO coordination in two oxidation states with a high level of CO activation (νCO = 1851 and 1751 cm–1). The local Fe coordination environment (2S, 1C, 1CO) is identical to that in the protein making this system a suitable benchmark. Computational studies find an unusual intermediate spin electronic configuration at the Fe sites promoted by the presence the carbyne ligand. This electronic feature is partly responsible for the high degree of CO activation in the reduced cluster.

S ubstrate activation at complex inorganic cofactors in enzyme active sites has raised fundamental questions about the role of the cluster structure on reactivity.For example, the challenging conversion of N 2 to NH 3 by nitrogenase enzymes occurs at FeMo cofactor (FeMoco) (M = Mo, V, or Fe), which comprises complex double cubane clusters with the MFe 7 S 9 C composition. 1,2−11 Only two CO-bound species of FeMoco and FeVco have been characterized structurally. 9,10,12,13−29 Only one type of FeS cluster with a single terminal CO ligand has been characterized, ligated by three carbene ligands. 30,31aving accessed a partial synthetic analogue 1 of the cluster core of FeMoco displaying a μ 3 -carbyne ligand with the WFe 3 S 3 CR composition, where W is the isoelectronic analogue of Mo, 32 we targeted the coordination of nitrogenase substrates (Scheme 1). 33Herein, we report the reactivity of 1 with isocyanides and CO, which affords an FeS cubane with a single terminal CO.We characterize this cluster in two oxidation states, which show a high level of CO activation, as observed in the low CO stretching frequency (1751−1851 cm −1 ) by IR spectroscopy.We employed isocyanides as isoelectronic analogues of CO and substrates of nitrogenase 34 that also allow for a more controlled reactivity.−38 Heating 2-t Bu in THF at 70 °C for 16 h leads to the formation of 3, where XRD and NMR studies are consistent with the loss of a t Bu radical (leaving an η 2 -nitrile ligand). 39While determining the protonation state of the N atom solely on the basis of XRD is inconclusive, the short C−N bond length of 1.205(6) Å Scheme 1. Syntheses of Clusters compared with ∼1.25 Å for η 2 -iminoacyl (see the Supporting Information for additional literature comparison and support by ATR IR spectroscopy) is indicative of an η 2 -nitrile motif. 40oss of the t Bu radical suggests a propensity for side-on nitrile binding, which is an intriguing observation in the context of the nitrogenase substrates displaying triple bonds, including N 2 , acetylene, and isocyanides. 41The conversion from 2-t Bu to 3, which involves the loss of a t Bu radical, formally represents one-electron oxidation of the WFe 3 metal core.In contrast to 2-t Bu, 2-Xyl is stable under the same conditions, which is consistent with a lower tendency to lose the more reactive aryl radical. 42ith 3 in hand, we explored reactions with CO.Cluster 3 reacts with 1 atm CO to form 4 within 5 min, which shows substitution of one bis(diisopropylamino)cyclopropenylidene (BAC) ligand with CO (83% yield, Scheme 1) in an uncommon instance of carbene lability. 43The average Fe− C(μ 3 ) distance remains similar to 2-t Bu and 3 at 1.95 Å, but the range for the individual bond lengths increases to 1.88− 2.00 Å (compared with 1.92−1.95Å in 2-t Bu and 1.95−1.96Å in 3), which suggests that the carbyne ligand, and potentially the carbide in FeMoco, has the ability to accommodate distinct electronic demands of different Fe centers through structural changes. 44This is in contrast to spectroscopic studies suggesting that the central carbide serves to maintain the rigid core structure. 8,45o the best of our knowledge, 4 is the only wellcharacterized example of a heterometallic MFe 3 S 3 (CR) cubane cluster bearing a single terminal CO ligand.This provides an opportunity for benchmarking the impact of structure and coordination environment relative to FeMoco.The THF solution IR spectrum of 4 displays a prominent peak at 1851 cm −1 , assigned as the C−O stretch (Figure 3) and confirmed by 13 CO labeling (ν 13CO exp = 1807 cm −1 , ν 13CO calc = 1810 cm −1 ), thereby suggesting highly activated CO.
To study the effects of cluster oxidation state on the level of CO activation, we reduced 4 with one equivalent of KC 8 or potassium naphthalenide to yield 4-K (S = 3/2, see the Supporting Information) (Scheme 1).As expected, the CO bond length increases upon reduction from 1.15(1) to 1.198(3) Å.The solution IR spectrum of 4-K shows two C− O bands at 1794 and 1751 cm −1 (Figure 3), which is consistent with the crystal structure of 4-K displaying CO−K + interactions disordered over two positions: terminal (36% occupancy) (assigned as 4-K terminal ) and η 2 (64% occupancy) (assigned as 4-K η2 ).These isomers are collectively referred to as 4-K.Chelation of K + with 18-crown-6 results in the formation of 4-K (18-crown-6).XRD shows that the K + ion is present in only one location and interacts end-on with the O atom of CO (Figure 2).In agreement, the IR spectrum shows a single band at 1782 cm −1 (Figure 3; ν 13CO exp = 1740 cm −1 ; ν 13CO calc = 1742 cm −1 ).The same band is observed upon treatment with [2.2.2]cryptand, thereby suggesting that the K + ion in 4-K(18-crown-6) does not impact CO activation substantially. 46oth 4-K and 4-K(18-crown-6) exhibit highly activated CO ligands coordinated to Fe in a terminal fashion.The interaction with K + in different binding modes affects the level of CO activation in the 1794 and 1751 cm −1 range.Previous computational work describes a semibridging CO ligand at Fe2 in FeMoco with a frequency of 1718 cm −1 , 47 very close to that assigned to the bridging CO in lo-CO at 1715 cm −1 . 48his is slightly lower than the typical values observed for μ 2 -CO ligands, which lie in the 1720−1850 cm −1 range. 49ydrogen bonding between the carbonyl oxygen and the nearby His195 residue is proposed to further activate CO. 47 Similarly, in 4-K, the K + cation can play the same role as the hydrogen bonding network and lower the C−O stretching frequency.Nevertheless, ν CO values below 1800 cm −1 are unprecedented for FeS clusters.For comparison, the CO adducts of N-heterocyclic carbene (NHC)-supported Fe 4 S 4 clusters reported by Suess and co-workers display C−O stretching frequencies of 1832 cm −1 for the [Fe 4 S 4 ] 0 and 1902 cm −1 for the [Fe 4 S 4 ] + states. 30The local coordination environment at each Fe (FeS 2 C in 4 and 4-K and FeS 3 in [Fe 4 S 4 ] +,0 ) and oxidation state distribution between different metal sites can contribute to the level of diatomic activation. 30,50,51n order to understand the electronic structure origin of the profound CO activation in these clusters, we employed computational methods using broken symmetry density functional theory (BS-DFT).Our computational procedure detailed in the Supporting Information accurately assigns the geometric, Mossbauer, and vibrational properties of 4 and 4-K.Here, we highlight the impact of the carbyne, W 3+ center, and a K + countercation with respect to the strong CO activation in 4-K.
The carbyne has three anionic lone pairs oriented along the Fe-bonding axes in its μ 3 -binding mode.The localized orbitals characterize the carbyne lone pairs as σ-donors that stabilize the intermediate spin (IS) state of the three formal Fe 2+ (S = 1) centers.Observing the IS state at the Fe sites that do not bind CO suggests that it is an innate property of the μ 3carbyne ligand.The IS state in Fe 2+ centers give full occupation of its π-backbonding orbitals, consistent with the increased CO activation in 4-K.In agreement, hyperfine sublevel correlation (HYSCORE) spectra of 4-K( 13 CO) show small hyperfine coupling to the 13 C center of CO {A( 13 C) = [−0.5,1.0, −0.5] MHz; see the Supporting Information}.A partially occupied Fe−CO backbonding orbital is expected to result in larger coupling. 5,52,53In comparison, Fe centers in FeS clusters are  13 CO-labeled species with ν 13CO in gray.The feature at 1830 cm −1 unchanged upon 13 CO labeling is assigned to BAC.
routinely assigned as high-spin because of their weak ligand field environment, such as the S = 3/2 state assigned to the CO-bound Fe 1+ by Suess and co-workers. 30urthermore, the Fe centers are preferentially ferromagnetically coupled, which results in the equal delocalization of two electrons among the three Fe atoms (Figure 4).This formally lowers the oxidation state of the CO-bound Fe site from its formal 2+ to 1.33+ charge and proportionately increases the other Fe centers to 2.33+; their resonance states are illustrated in the Supporting Information.This is analogous to the net Fe 2.5+ oxidation state resulting from the equal delocalization of one electron between two Fe sites in formal Fe 2+ −Fe 3+ dimers. 54This pairwise delocalization supports a reduced state at the CO-bound center that is otherwise inaccessible under biological conditions.Similarly, redox disproportionation has been proposed in previously reported [Fe 6 (μ 6 -C)(CO) 18 ] and Fe 4 S 4 (CO)(IMes) 3 clusters, where Fe sites of different oxidation states are within close proximity. 30,55he anionic charge of 4 − supports strong noncovalent interactions with its countercation.The geometry optimization of 4-K preferentially binds K + in an η 2 -conformation with respect to the CO bond.The calculated CO stretching frequency decreases from 1800 cm −1 without K + to 1756 cm −1 , which is consistent with the distinct vibrational modes observed in the IR spectrum of 4-K.The electronic structure of the cluster is not impacted by K coordination, thereby suggesting that it is a purely ionic interaction that stabilizes the π-bonding of the CO ligand.
The CO lone pair can overlap with orbitals arising from the Fe−W interaction assigned as purely covalent in 4 − on the basis of the localized orbitals (see Figure S34 for a graphical representation).The Fe−W covalent interaction redistributes electron density between the metal centers promoting the electrostatic attraction with the CO lone pair and consequently also enhances the π*-backbonding discussed above. 56,57The other Fe centers exhibit bonding characters that are intermediate of a covalent and magnetic interaction, analogous to bonding properties detailed in the Mo 3+ heteroatom of FeMoco. 58,59In contrast, this is not observed for the cluster reported by Suess and co-workers 30 because of the comparatively weak bonding interactions between Fe sites.Overall, these factors contribute to the stronger CO activation in 4 − compared with these reported clusters with an average metal oxidation state of 2+, despite the higher average metal oxidation state of 2.25+ in 4 − . 30n summary, we have reported a series of heterometallic WFe 3 S 3 CR cubanes and demonstrated several types of organometallic transformations and binding modes that are rare for iron−sulfur clusters.These compounds show C−C coupling, along with side-on binding of an organic nitrile moiety at one Fe site.Furthermore, we characterized the first example of a heterometallic iron−sulfur cluster with a single terminally bound, highly activated CO ligand in two oxidation states.Computation suggests an unusual carbyne-promoted intermediate spin electronic configuration at all Fe sites, along with a low oxidation state of 1.33+ for Fe(CO) in 4 − .This electron configuration affords full occupancy of the two πback-bonding orbitals to CO, which are responsible for the high level of CO activation in the reduced clusters.The negative charge of the cluster and the metal−metal covalency were found computationally to also impact CO activation.These findings provide a set of parameters to evaluate in future studies for the conversion of substrates in nitrogenase.
General methods, synthetic procedures, product isolation and characterization, NMR spectra, structural information, and computational methods (PDF)

Figure 4 .
Figure 4. Local oxidation and spin states of the metal centers of 4 − (S = 3/2) with respect to the Mulliken spin population of their PMlocalized orbitals (Figures S34−36).The curved green arrow denotes a pair of electrons that are equally delocalized among the Fe centers (illustrated in the inset) with respect to its localized spin density.The degenerate Fe−CO π-bonding interactions are shown at the bottom with respect to their localized orbitals.